OP0017 ACTIVE LUPUS NEPHRITIS PATIENTS DISPLAY AN INCREASED PROPORTION OF RECENTLY ACTIVATED NAÏVE DNA-REACTIVE B CELLS
Authors: K. Wangriatisak, F. Faustini, R. Kumar, C. De Vries, P. Pisitkun, P. Chootong, V. Malmström, I. Gunnarsson
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Altered composition of B cell compartments is known in patients with systemic lupus erythematosus (SLE). However, similar characterisation of the disease-associated autoreactive B cells remains scarce. Elucidating the autoreactive B cell subsets and their association to lupus manifestations may provide tools for monitoring, biomarkers and even identifying possible targets for future therapeutic intervention. <h3>Objectives</h3> To investigate phenotypic characteristics of extrafollicular B cell subsets in a cohort of SLE patients. <h3>Methods</h3> Twelve SLE patients, including nine with positive anti-dsDNA antibodies (75%), and ten healthy controls (HCs) were recruited for this study. Data was represented as median and interquartile range (IQR). To identify DNA-reactive B cells, surrogate peptide (DWEYSVWLSN) that serves as dsDNA mimotope was used, as previously shown (1, 2). The phenotype of peripheral B cell subsets and DNA-reactive B cells was analyzed by spectral flow cytometric analysis. The correlations between different B cell populations and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, clinical manifestations and laboratory data were assessed. <h3>Results</h3> In SLE patients, median SLEDAI-2K score was 14.5 (4.5-19.5), median age and disease duration were 32 (29-48.5) and 10 (1-13) years, respectively. Eight patients presented with lupus nephritis (LN), with proliferative (class III/IV, n = 2), membranous (class V, n = 1) and mixed histological pattern (class III &amp; V, n = 3 and class IV &amp; V, n = 2). Phenotypic analysis showed an expansion of recently activated, so called activated naïve (aNAV: CD11c<sup>+</sup>CXCR5<sup>-</sup>CD21<sup>-</sup>CD27<sup>-</sup>IgD<sup>+</sup>, <i>p</i> = 0.0005), double negative 2 B cells (DN2: CD11c<sup>+</sup>CXCR5<sup>-</sup>CD21<sup>-</sup>CD27<sup>-</sup>IgD<sup>-</sup>, <i>p</i> = 0.0001) and double negative 3 B cells (DN3: CD11c<sup>-</sup>CXCR5<sup>-</sup>CD21<sup>-</sup>CD27<sup>-</sup>IgD<sup>-</sup>, <i>p</i> = 0.005) in the blood of the total SLE patient group compared to HC, with aNAV B cells frequency being higher in LN patients (Figure 1). DNA-reactive B cells were mostly represented by an aNAV phenotype (CD11c<sup>+</sup>CXCR5<sup>-</sup>CD21<sup>-</sup>) which overexpressed CD11c and CD80. Moreover, a significantly increased percentage of such autoreactive B cells was observed in LN patients (median (IQR) 0.13% (0.095-0.160) compared with non-LN patients (median (IQR) 0.056% (0.042-0.070), p = 0.0357). The percentage of aNAV B cells were positively correlated with disease activity measured as SLEDAI-2K index (<i>r</i> = 0.619, <i>p</i> = 0.036). These aNAV B cells also had a positive correlation with DN2 (<i>r</i> = 0.578, <i>p</i> = 0.049) and plasmablasts (<i>r</i> = 0.420, <i>p</i> = 0.041). <h3>Conclusion</h3> Our data show that aNAV B cells are expanded in SLE and display autoreactivity to dsDNA. The association between the frequency of aNAV B cells and disease activity, and with lupus nephritis suggests that these cells may be used as a monitoring biomarker in the disease. <h3>References</h3> [1] Jacobi AM, Zhang J, Mackay M, Aranow C, Diamond B. Phenotypic characterization of autoreactive B cells--checkpoints of B cell tolerance in patients with systemic lupus erythematosus. PLoS One. 2009;4(6):e5776. [2] Wangriatisak K, Thanadetsuntorn C, Krittayapoositpot T, <i>et al</i>. The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients. <i>Arthritis Res Ther</i> 2021;23:179. <h3>Disclosure of Interests</h3> None Declared.